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• The present paper is of significant relevance in finding novel and effective weapons originating from Traditional Chinese Medicine and Ayurveda to address the molecular heterogeneity of cancer and at the same time projecting Withania somnifera (WS) as a potent phytoestrogen. • Also significant advancements in pharmacology and drug technology aimed at improving the efficacy of cancer therapies and extending the life expectancy of patients diagnosed with malignancy. It emphasizes the gender disparity in breast cancer occurrence, with the female gender being the primary risk factor. • Withania somnifera (WS), commonly known as Indian ginseng, has garnered attention for its traditional use in treating various ailments. Recent research has demonstrated promising anti-breast cancer properties of WS and its phytoconstituents. These findings suggest the potential of WS as both a prophylactic and therapeutic adjunct to standard breast cancer treatments. The review delves into the experimental evidence supporting the use of WS in breast cancer management, shedding light on its molecular mechanisms and targets. • The review explores the broader implications of WS in hormonally-induced cancers, including ovarian, uterine, and cervical cancers. By elucidating the multiple molecular mechanisms through which WS acts against these cancers, the review aims to provide insights into breast cancer progression and metastasis. • Moreover, WS is not recognized as a phytoestrogen-rich herb, however, some studies suggests it may exhibit estrogenic properties. These potential highlights include its ability to modulate hormonal balance, support reproductive health and alleviate symptoms associated with hormonal imbalances. Also, a few papers of this type have been published in the journal in the last few years. Therefore, the present review highlights the unexplored potential of WS, which might significantly contribute towards the pleiotropic potential of WS. Major significant advancements in pharmacology and drug technology have been made to heighten the impact of cancer therapies, improving the life expectancy of subjects diagnosed with malignancy. Statistically, 99% of breast cancers occur in women while 0.5–1% occur in men, the female gender being the strongest breast cancer risk factor. Despite several breakthroughs, breast cancer continues to have a worldwide impact and is one of the leading causes of mortality. Additionally, resistance to therapy is a crucial factor enabling cancer cell persistence and resurgence. As a result, the search and discovery of novel modulatory agents and effective therapies capable of controlling tumor progression and cancer cell proliferation is critical. Withania somnifera (L.) Dunal (WS), commonly known as Indian ginseng, has long been used traditionally for the treatment of several ailments in the Indian context. Recently, WS and its phytoconstituents have shown promising anti-breast cancer properties and, as such, can be employed as prophylactic as well as therapeutic adjuncts to the main line of breast cancer treatment. The present review is an attempt to explore and provide experimental evidences in support of the prophylactic and therapeutic potential of WS in breast cancer, along with a deeper insight into the multiple molecular mechanisms and novel targets through which it acts against breast and other hormonally-induced cancers viz. ovarian, uterine and cervical. This exploration might prove crucial in providing better understanding of breast cancer progression and metastasis and its use as an adjunct in improving disease prognosis and therapeutic outcome. [ABSTRACT FROM AUTHOR]

• CAR-T therapy offers durable remissions in refractory hematological malignancies. • Meta-analyses show significant efficacy in various hematologic cancers. • CAR T-cell therapy improves quality of life for blood cancer patients. • Encouraging results in CD22-targeting CAR T-cell therapy for B-cell malignancies. • Long-term studies reveal durable remissions but also persistent adverse effects. Chimeric Antigen Receptor T-cell (CAR-T) therapy has emerged as a groundbreaking and highly promising approach for the management of cancer. This paper reviews the efficacy of CAR-T therapy in the treatment of various hematological malignancies, also, with a mention of its effect on solid tumors, for which they have not received FDA approval yet. Different common and uncommon side effects are also discussed in this paper, with attention to the effect of each drug separately. By reviewing the recommendations of the FDA for CAR-T therapy research, we have extensively discussed dose-limiting toxicities. This further highlights the need for precise dosing strategies, striking a balance between therapeutic benefits and potential risks. Additionally, we reviewed the long-term follow-up of patients receiving CAR-T therapy to gain valuable insights into response durability and late-onset effects. [ABSTRACT FROM AUTHOR]

[Display omitted] • CKLF1 shows various effects on different types of cells involved in cardiovascular and cerebrovascular diseases. • CKLF1 plays complex and dynamic roles in diverse cardiovascular and cerebrovascular diseases. • Targeting CKLF1 has therapeutic potential for treating cardiovascular and cerebrovascular diseases. Chemokine like factor 1 (CKLF1) is a novel atypical chemokine, playing a crucial role in cardiovascular and cerebrovascular diseases (CCVDs) demonstrated by a growing body of works. In cardiovascular diseases including atherosclerosis and myocardial infarction, meanwhile in cerebrovascular diseases such as ischemic stroke and hemorrhagic stroke, the expression levels of CKLF1 change markedly, which triggers downstream signaling pathways by binding with its functional receptors, and then exerts multiple effects to participate in the occurrence and development of these CCVDs. The functional roles of CKLF1 are dynamic and CKLF1 may act as a double-edged sword. The CCVDs-promoting role is related to recruiting inflammatory cells, enhancing the proliferation of vascular smooth muscle cells and endothelial cells, while the CCVDs-suppressing role may correlate with migration of nerve cells and promotion of hematopoietic stem cell proliferation which contributes to disease recovery. Based on this, the paper intends to review expression shifts, potential roles, and molecular mechanisms of CKLF1 in CCVDs, and the current status of CKLF1 targeted therapeutic strategies is also included. We hope this review may provide a valuable reference for using CKLF1 as a diagnostic and prognostic biomarker for CCVDs or developing novel treatments. [ABSTRACT FROM AUTHOR]

• VISTA is an inhibitory immune checkpoint that acts as a ligand or receptor to exert immunosuppressive effects. • Abnormal overexpression of VISTA in gynecological tumors promotes tumor progression. Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment but has shown limited efficacy in gynecologic cancers. VISTA (V-domain Ig suppressor of T-cell activation), a member of the B7 family, is emerging as another checkpoint that regulates the anti-tumor immune responses within the tumor microenvironment. This paper reviews the structure, expression, and mechanism of action of VISTA. Furthermore, it highlights recent advances in VISTA-blocking therapies and their potential in improving outcomes for patients with gynecologic cancers. By understanding the role of VISTA in mediating the immune evasion of gynecologic tumors, we can develop more effective combinatory treatment strategies that could overcome resistance to current ICB therapies. [ABSTRACT FROM AUTHOR]

• This paper provides a new theoretical framework from disease-related biomolecules to treatment progress. • This paper further collected evidence for the conclusion that psoriasis is an autoimmune disease. • This paper summarizes the development of biologic therapies for psoriasis and psoriatic arthritis. Over the past half century, psoriasis is considered as an immune-mediated inflammatory skin disease with the combined hallmarks of autoimmunity and autoinflammation, according to growing volumes of clinical and experimental findings. There is currently no cure for psoriasis, current treatment strategies focus on symptom control, disease minimization, and patient's quality of life enhancement. To meet these challenges, it keeps imperative to discover potential biomarkers, so that not only can they be used for the prediction and monitoring of psoriasis disease in clinic, but also can provide novel therapeutic targets or treatment strategies for psoriasis sufferers. This review systematically demonstrates the research progress of psoriasis-related biomarkers and elaborates their related mechanisms in the pathological development of psoriasis and psoriatic arthritis. In addition, we summarize the development of biologic therapies for psoriasis and psoriatic arthritis in order to drive the broader discussion of psoriasis as an autoimmune-mediated inflammatory skin disease. [ABSTRACT FROM AUTHOR]

• CD24 and CSC: Few previous studies have summarized the relationship between CD24 and corresponding cancer stem cells. This review summarizes the reported CD24-related tumor stem cells so far. • CD24 and tumor progression: CD24, as a kind of innate immune checkpoints, not only can be mediated tumor cell immune escape, also can promote the proliferation and metastasis of tumor cells, this paper summarizes the current related studies of CD24 promote tumor progression, indicate its potential as a cancer related molecules, provides a theoretical basis for future targeted therapies. • CD24 is involved in drug resistance of tumor cells: Chemotherapy resistance is a common problem in tumor treatment. Studies have found that CD24 may promote tumor drug resistance after chemotherapy. This paper summarizes the post chemotherapy drug resistance of tumors related to CD24 for the first time. The CD24 protein is a heat-stable protein with a small core that undergoes extensive glycosylation. It is expressed on the surface of various normal cells, including lymphocytes, epithelial cells, and inflammatory cells. CD24 exerts its function by binding to different ligands. Numerous studies have demonstrated the close association of CD24 with tumor occurrence and progression. CD24 not only facilitates tumor cell proliferation, metastasis, and immune evasion but also plays a role in tumor initiation, thus, serving as a marker on the surface of cancer stem cells (CSCs). Additionally, CD24 induces drug resistance in various tumor cells following chemotherapy. To counteract the tumor-promoting effects of CD24, several treatment strategies targeting CD24 have been explored, such as the use of CD24 monoclonal antibodies (mAb) alone, the combination of CD24 and chemotoxic drugs, or the combination of these drugs with other targeted immunotherapeutic techniques. Regardless of the approach, targeting CD24 has demonstrated significant anti-tumor effects. Therefore, the present study focuses on anti-tumor therapy and provides a comprehensive review of the structure and fundamental physiological function of CD24 and its impact on tumor development, and suggests that targeting CD24 may represent an effective strategy for treating malignant tumors. [ABSTRACT FROM AUTHOR]

• Osteosarcoma is the most common malignant bone tumor in children and adolescents. • The tumor microenvironment releases substances that promote tumor cell metastasis. • The paper reviews research on osteosarcoma metastasis and the tumor microenvironment. Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. It is characterized by a rapid progression, poor prognosis, and early pulmonary metastasis. Over the past 30 years, approximately 85% of patients with osteosarcoma have experienced metastasis. The five-year survival of patients with lung metastasis during the early stages of treatment is less than 20%. The tumor microenvironment (TME) not only provides conditions for tumor cell growth but also releases a variety of substances that can promote the metastasis of tumor cells to other tissues and organs. Currently, there is limited research on the role of the TME in osteosarcoma metastasis. Therefore, to explore methods for regulating osteosarcoma metastasis, further investigations must be conducted from the perspective of the TME. This will help to identify new potential biomarkers for predicting osteosarcoma metastasis and assist in the discovery of new drugs that target regulatory mechanisms for clinical diagnosis and treatment. This paper reviews the research progress on the mechanism of osteosarcoma metastasis based on TME theory, which will provide guidance for the clinical treatment of osteosarcoma. [ABSTRACT FROM AUTHOR]

• Aptamer-mediated nanomedicines could enhance the accuracy of drug delivery and target drug delivery to tumor sites, reducing side effects. • Aptamer-mediated photodynamic therapy could more precisely deliver photosensitizers to tumor cells, reducing toxicity to normal tissues. • Aptamer-mediated photothermal therapy could enable the light source to more accurately locate and convert light energy into heat energy, causing local temperature rise, thereby eliminating cancer cells and effectively reducing the adverse effects on normal tissues. • Immunotherapy combined with aptamers could more accurately identify and modulate immune cells in the tumor microenvironment, enhancing anti-tumor immune responses and protecting normal tissues. The treatment of tumors still faces considerable challenges. While conventional treatments such as surgery, chemotherapy, and radiation therapy provide some curative effects, their side effects and limitations highlight the importance of finding more precise treatment strategies. Aptamers have become an important target molecule in the field of drug delivery systems due to their good affinity and targeting, and they have gradually become an important link from basic research to clinical application. In this paper, we discussed the latest progress of aptamer-mediated nanodrugs, as well as aptamer-mediated photodynamic therapy, photothermal therapy, and immunotherapy strategies for tumor treatment, and explored the possibility of aptamer-mediated therapy for accurate tumor treatment. The purpose of this review is to provide novel insights for treating tumors with aptamer-mediated therapies by summarizing these innovative strategies, thereby ultimately enhancing the therapeutic efficacy for cancer patients. [ABSTRACT FROM AUTHOR]

• Ultrasound combined with tumor immunotherapy made encouraging new progress in both basic research and clinical treatment. • Ultrasound can increase the delivery of immunomodulatory substances and enhance the effect of immunotherapy. • Ultrasound can be used to improve the body's immune response to tumors. Immunotherapy has become a revolutionary method for treating tumors, offering new hope to cancer patients worldwide. Immunotherapy strategies such as checkpoint inhibitors, chimeric antigen receptor T-cell (CAR-T) therapy, and cancer vaccines have shown significant potential in clinical trials. Despite the promising results, there are still limitations that impede the overall effectiveness of immunotherapy; the response to immunotherapy is uneven, the response rate of patients is still low, and systemic immune toxicity accompanied with tumor cell immune evasion is common. Ultrasound technology has evolved rapidly in recent years and has become a significant player in tumor immunotherapy. The introductions of high intensity focused ultrasound and ultrasound-stimulated microbubbles have opened doors for new therapeutic strategies in the fight against tumor. This paper explores the revolutionary advancements of ultrasound combined with immunotherapy in this particular field. [ABSTRACT FROM AUTHOR]

• The new oral vaccine NC8/Δalr-pCXa-VP6-S and NC8/Δalr-pCXa-VP6-pFc-S was successfully developed. • NC8/Δalr-pCXa-VP6-S and NC8/Δalr-pCXa-VP6-pFc-S can activate host immunity. • NC8/Δalr-pCXa-VP6-S and NC8/Δalr-pCXa-VP6-pFc-S can protect the piglets against infection with PEDV. Porcine rotavirus (PoRV) poses a threat to the development of animal husbandry and human health, leading to substantial economic losses. VP6 protein is the most abundant component in virus particles and also the core structural protein of the virus. Firstly, this study developed an antibiotic-resistance-free, environmentally friendly expression vector, named asd-araC-PBAD-alr (AAPA). Then Recombinant Lactiplantibacillus plantarum (L. plantarum) strains induced by arabinose to express VP6 and VP6-pFc fusion proteins was constructed. Subsequently, This paper discovered that NC8/Δalr-pCXa-VP6-S and NC8/Δalr-pCXa-VP6-pFc-S could enhance host immunity and prevent rotavirus infection in neonatal mice and piglets. The novel recombinant L. plantarum strains constructed in this study can serve as oral vaccines to boost host immunity, offering a new strategy to prevent PoRV infection. [ABSTRACT FROM AUTHOR]

• E-MPBs shows sustained cellular uptake by microglia. • E-MPBs exhibits anti-ROS and anti-inflammation properties against M1 microglia. • E-MPBs develops a novel nanoplatform for SCI. Developing biomimetic nanoparticles without off-target side-effects remains a major challenge in spinal cord injury (SCI) immunotherapy. In this paper, we have conducted a drug carrier which is biocompatible macrophages-exocytosed exosome-biomimetic manganese (Mn)-iron prussian blue analogues (MPBs) for SCI immunotherapy. Exosome-sheathed MPBs (E-MPBs) exhibit promoted microglia accumulation, alleviation from H 2 O 2 -induced microenvironment and inhibition of apoptosis and inflammation in vitro. In addition, E-MPBs possessed significant tissue repair and neuroprotection in vivo. These properties endowed E-MPBs with great improvement in vivo in function recovery, resulting in anti-neuroinflammation activity and excellent biocompatibility in mice SCI model. As a promising treatment for efficient SCI immunotherapy, these results demonstrate the use of exosome-sheathed biomimetic nanoparticles exocytosed by anti-inflammation cells is feasible. [ABSTRACT FROM AUTHOR]

• A discussion of research advances in the use of genetically engineered bacteria in conjunction with traditional modalities for the treatment of tumors, such as immunotherapy, chemotherapy, and radiation therapy. • An overview of common modifications of genetically engineered bacteria. • A discussion of the progress of clinical trials related to genetically engineered bacteria. Finding novel therapeutic modalities, improving drug delivery efficiency and targeting, and reducing the immune escape of tumor cells are currently hot topics in the field of tumor therapy. Bacterial therapeutics have proven highly effective in preventing tumor spread and recurrence, used alone or in combination with traditional therapies. In recent years, a growing number of researchers have significantly improved the targeting and penetration of bacteria by using genetic engineering technology, which has received widespread attention in the field of tumor therapy. In this paper, we provide an overview and assessment of the advancements made in the field of tumor therapy using genetically engineered bacteria. We cover three major aspects: the development of engineered bacteria, their integration with other therapeutic techniques, and the current state of clinical trials. Lastly, we discuss the limitations and challenges that are currently being faced in the utilization of engineered bacteria for tumor therapy. [ABSTRACT FROM AUTHOR]

With the development of the social economy, unhealthy living habits and eating styles are gradually affecting people's health in recent years. As a chronic liver disease, NAFLD is deeply affected by unhealthy living habits and eating styles and has gradually become an increasingly serious public health problem. As a protein complex in clinical research, the inflammasomes play a crucial role in the development of NAFLD, atherosclerosis, and other diseases. This paper reviews the types, composition, characteristics of inflammasomes, and molecular mechanism of the inflammasome in NAFLD. Meanwhile, the paper reviews the drugs and non-drugs that target NLRP3 inflammasome in the treatment of NAFLD in the past decades. we also analyzed and summarized the related experimental models, mechanisms, and results of NAFLD. Although current therapeutic strategies for NAFLD are not effective, we expect that we will be able to find an appropriate treatment to address this problem in the future with further research on inflammasome. [ABSTRACT FROM AUTHOR]

• Sepsis is the leading cause of death in ICU patients and an effective treatment is still lacking. Therefore, research in this area is necessary and of great value. • This review summarizes the latest findings and gaps related to the NLRP3 inflammasome, a key player in the innate immune system and the pathological process of sepsis. • Many studies suggested that targeting the NLRP3 inflammasome coule be applied to treat sepsis and sepsis-related organ dysfunction. Sepsis is the host immune imbalance following infection and leads to organ dysfunction, with highly complicated pathophysiology. To date, sepsis still lacks effective therapies with high mortality rates. Recently, numerous studies have highlighted the potential of NLRP3 inflammasome as a therapeutic target during sepsis. NLRP3 inflammasome is a protein complex that could induce the activation of caspase-1 and the following release of pro-inflammatory cytokines such as IL-1β and IL-18. It was demonstrated that NLRP3 inflammasome was involved in the development and progression of sepsis. In contrast, inhibition of NLRP3 inflammasome activation could mitigate the inflammatory response, protect organ function, and improve outcomes and mortality. This paper illustrated the activation pathways of the NLRP3 inflammasome and its possible molecular mechanisms in the pathophysiology of sepsis. Meanwhile, the beneficial effects of inhibiting NLRP3 activation in sepsis-related organ damage were also presented. In addition, the diverse role of NLRP3 inflammasome in bacterial clearance was addressed. Of note, several herbal extracts targeting NLRP3 inflammasome in the treatment of sepsis were emphasized. We hope that this paper could provide a basis for further drug research targeting NLRP3 inflammasome. [ABSTRACT FROM AUTHOR]

• In the early stage of cirrhosis, there seems to be a possibility of cirrhosis reversal. • The development of cirrhosis is related to the intestinal microbiota and activation of toll-like receptors (TLRs) pathways, which could regulate cell proliferation, apoptosis, expression of the hepatomitogen epiregulin, and liver inflammation. • In this paper, we first reviewed the dynamic change of intestinal microbiota and TLRs during cirrhosis progression. And further discussed the interaction between them and potential therapeutic targets to reverse early staged cirrhosis. • The interference of toll-like receptors (TLRs) and its intracellular signaling pathway can regulate the liver inflammatory response and cirrhosis process. • Drug treatment of intestinal dysbiosis and TLRs activation may slow cirrhosis progression. • With the further study of intestinal microbiota and TLRs on the progression of cirrhosis, it offers a new way of preventing and treating inflammatory response and fibrosis diseases. Cirrhosis is a progressive chronic liver disease caused by one or more causes and characterized by diffuse fibrosis, pseudolobules, and regenerated nodules. Once progression to hepatic decompensation, the function of the liver and other organs is impaired and almost impossible to reverse and recover, which often results in hospitalization, impaired quality of life, and high mortality. However, in the early stage of cirrhosis, there seems to be a possibility of cirrhosis reversal. The development of cirrhosis is related to the intestinal microbiota and activation of toll-like receptors (TLRs) pathways, which could regulate cell proliferation, apoptosis, expression of the hepatomitogen epiregulin, and liver inflammation. Targeting regulation of intestinal microbiota and TLRs pathways could affect the occurrence and development of cirrhosis and its complications. In this paper, we first reviewed the dynamic change of intestinal microbiota and TLRs during cirrhosis progression. And further discussed the interaction between them and potential therapeutic targets to reverse early staged cirrhosis. [ABSTRACT FROM AUTHOR]

• Knockdown of IFIT3 represses M1 polarization. • IFIT3 does not affect IL-4 induced M2 polarization of microglia. • Knockdown of IFIT3 blocks the activation of STAT1 and NF-ĸB pathways. • IFIT3 regulates the polarization of microglia, thereby facilitating MS. The key to the treatment of multiple sclerosis (MS) is to promote the transition from inflammation-induced demyelination to remyelination. Polarization of microglia towards M1 or M2 phenotype is critical in this transition. Interferon induced protein with tetratricopeptide repeats 3 (IFIT3) is involved in inflammatory reaction and up-regulated in M1-polarized macrophages. However, its effect on microglia during MS has not been reported. In this paper, we demonstrated the important role of IFIT3 in selectively regulating microglia polarization. The expression of IFIT3 was increased when microglia were polarized towards M1, but did not change under M2 polarization. The knockdown of IFIT3 selectively inhibited M1 polarization, while M2 polarization was not affected by IFIT3 silencing. Furthermore, the activation of signal transducer and activator of transcription 1 (STAT1) and nuclear factor kappa-B (NF-ĸB) signaling in M1 polarized microglia was suppressed by downregulating IFIT3. In experimental autoimmune encephalitis (EAE) mice, an animal model of MS, IFIT3 expression was upregulated. The disease progression, inflammatory infiltration and demyelination in the EAE mice were alleviated by silencing IFIT3. The inhibitory effects of IFIT3 knockdown on M1 polarization and STAT1 and NF-ĸB pathways were also confirmed in the spinal cord of EAE mice. In summary, our findings suggest that IFIT3 selectively intensified microglia polarization towards the pro-inflammatory M1 phenotype, and may contribute to the progression of MS. [ABSTRACT FROM AUTHOR]

• ECM imbalance plays an important role in arthritis disease and is an effective intervention. • ECM affects synovium mainly through its components and related signaling pathways. • ECM in synovium offers promise for the treatment and prevention of arthritis. Extracellular matrix (ECM) is a three-dimensional network entity composed of extracellular macromolecules. ECM in synovium not only supports the structural integrity of synovium, but also plays a crucial role in regulating homeostasis and damage repair response in synovium. Obvious disorders in the composition, behavior and function of synovial ECM will lead to the occurrence and development of arthritis diseases such as rheumatoid arthritis (RA), osteoarthritis (OA) and psoriatic arthritis (PsA). Based on the importance of synovial ECM, targeted regulation of the composition and structure of ECM is considered to be an effective measure for the treatment of arthritis disease. This paper reviews the current research status of synovial ECM biology, discusses the role and mechanism of synovial ECM in physiological status and arthritis disease, and summarizes the current strategies for targeting synovial ECM to provide information for the pathogenesis, diagnosis and treatment of arthritis disease. [ABSTRACT FROM AUTHOR]

• Necroptosis as a form of programmed necrotic cell death played a role in intervertebral disc degeneration(IVDD). • The core components of the necrosome are the RIPK1, RIPK3 and MLKL. • Necroptosis occurred in different types of cells in intervertebral disc. • Targeting necroptosis had potential therapeutic value for the treatment of in IVDD. Intervertebral disc degeneration (IVDD) is a complex pathological condition associated with the development of low back pain. Despite numerous studies, the specific molecular mechanisms underlying IVDD remain unclear. At the cellular level, IVDD involves a series of changes, including cell proliferation, cell death, and inflammation. Of these, cell death plays a critical role in the progression of the condition. In recent years, necroptosis has been identified as a new form of programmed cell death (PCD). Necroptosis can be activated by ligands of death receptors, which then interact with RIPK1, RIPK3 and MLKL and lead to necrosome formation.. According to various previous studies, the necroptosis related pathway is activated in IVDD, and plays a significant role in the pathogenesis of IVDD. Furthermore, necroptosis may serve as a target for the IVDD treatment. Recently, several studies have reported the role of necroptosis in IVDD, but few studies have summarized the association between IVDD and necroptosis. The review gives a brief summary of the research progress of necroptosis, and discusses strategies and mechanisms that target necroptosis in IVDD. Lastly, matters needing attention in the necroptosis targeted therapy of IVDD are put forward at last. To the best of our knowledge, the review paper is the first one that integrates current research about the impact of necroptosis on IVDD, and contributes to the future therapy of IVDD from new perspectives. [ABSTRACT FROM AUTHOR]

• This paper describes the basic structure of CXCL1 and CXCR2 and the combination between them. CXCL1/CXCR2 is widely expressed in central and peripheral systems. • CXCL1/CXCR2 recruits inflammatory cells to the lesion site, causing an inflammatory response at the lesion site. • CXCL1/CXCR2 in the central nervous system can cause the development of inflammation, pain, depression, and Alzheimer's disease, but it can also inhibit the development of Alzheimer's disease in certain ways. • CXCL1/CXCR2 causes pain in the peripheral nervous system through multiple pathways. • CXCL1/CXCR2 are involved in cancer metastasis through the peripheral nervous system. The C-X-C chemokine ligand (CXCL) 1 and its receptor C-X-C chemokine receptor (CXCR) 2 are widely expressed in the peripheral nervous systems (PNS) and central nervous systems (CNS) and are involved in the development of inflammation and pain after various nerve injuries. Once a nerve is damaged, it affects not only the neuron itself but also lesions elsewhere in its dominant site. After the CXCL1/CXCR2 axis is activated, multiple downstream pathways can be activated, such as c-Raf/MAPK/AP-1, p-PKC-μ/p-ILK/NLRP3, JAK2/STAT3, TAK1/NF-κB, etc. These pathways in turn mediate cellular motility state or cell migration. CXCR2 is expressed on the surface of neutrophils and monocytes/macrophages. These cells can be recruited to the lesion through the CXCL1/CXCR2 axis to participate in the inflammatory response. The expression of CXCR2 in neurons can activate some pathways in neurons through the CXCL1/CXCR2 axis, thereby causing damage to neurons. CXCR2 is also expressed in astrocytes, and when CXCR2 activated, it increases the number of astrocytes but impairs their function. Since inflammation can occur at almost any site of injury, elucidating the mechanism o f CXCL1/CXCR2 axis' influence on inflammation may provide a favorable target for clinical treatment. Therefore, this article reviews the research progress of the CXCL1/CXCR2 axis in neurological diseases, aiming to provide a more meaningful theoretical basis for the treatment of neurological diseases. [ABSTRACT FROM AUTHOR]

• Rapid metabolism and some allergic reactions greatly limit the clinical application of SIN. • Compensating for its limitations and reducing side effects may enable sin to be better applied in the clinic. • SIN has great therapeutic potential in treating autoimmune diseases. • SIN in combination with DMARDs has great potential. Autoimmune diseases (ADs), with significant effects on morbidity and mortality, are a broad spectrum of disorders featured by body's immune responses being directed against its own tissues, resulting in chronic inflammation and tissue damage. Sinomenine (SIN) is an alkaloid isolated from the root and stem of Sinomenium acutum which is mainly used to treat pain, inflammation and immune disorders for centuries in China. Its potential anti-inflammatory role for treating immune-related disorders in experimental animal models and in some clinical applications have been reported widely, suggesting an inspiring application prospect of SIN. In this review, the pharmacokinetics, drug delivery systems, pharmacological mechanisms of action underlying the anti-inflammatory and immunomodulatory effects of SIN, and the possibility of SIN as adjuvant to disease-modifying anti-rheumatic drugs (DMARDs) therapy were summarized and evaluated. This paper aims to reveal the potential prospects and limitations of SIN in the treatment of inflammatory and immune diseases, and to provide ideas for compensating its limitations and reducing the side effects, and thus to make SIN better translate to the clinic. [ABSTRACT FROM AUTHOR]

• Docetaxel boosted anticancer effects of NK cells and CD8 + T lymphocytes. • Docetaxel stimulated the recruitment of tumor-associated macrophages. • Targeting some molecules such as PD-1 enhanced the anticancer activity of docetaxel. There are several interactions within the tumor microenvironment (TME) that affect the response of cancer cells to therapy. There are also a large number of cells and secretions in TME that increase resistance to therapy. Following the release of immunosuppressive, pro-angiogenic, and metastatic molecules by certain cells such as tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and cancer cells, immune evasion, angiogenesis, and metastasis may be induced. However, natural killer (NK) cells and cytotoxic CD8 + T lymphocytes (CTLs) can responsively release anticancer molecules. In addition, anticancer drugs can modulate these cells and their interactions in favor of either cancer resistance or therapy. Docetaxel belongs to taxanes, a class of anti-tumor drugs, which acts through the polymerization of tubulin and the induction of cell cycle arrest. Also, it has been revealed that taxanes including docetaxel affect cancer cells and the other cells within TME through some other mechanisms such as modulation of immune system responses, angiogenesis, and metastasis. In this paper, we explain the basic mechanisms of docetaxel interactions with malignant cells. Besides, we review the diverse effects of docetaxel on TME and cancer cells in consequence. Lastly, the modulatory effects of docetaxel alone or in conjunction with other anticancer agents on anti-tumor immunity, cancer cell resistance, angiogenesis, and metastasis will be discussed. [ABSTRACT FROM AUTHOR]

• Salmeterol was predicted to have activity against influenza A virus by using the network proximity analysis. • Salmeterol inhibited the activity of three IAV strains in the MDCK cells. • Salmeterol decreased the expression level of influenza A M2 and IFITM3 and inhibited the formation of NLRP3 inflammasome in infected mice. • Salmeterol increased the ratio of CD4+/CD8+ to regulate the imbalance of immune system in mice caused by viral infection. • Salmeterol protected A549 cells from cytopathic effect and reduced the production of inflammasome by decreasing the expression of RIG-1. Influenza A virus (IAV) is the most harmful pathogen to human beings among the various subtypes of influenza virus, which can lead to immune response, cause serious inflammation and damage to the lung. Salmeterol is a candidate compound with anti-IAV activity screened by virtual network proximity predication. In this paper, we further evaluated the pharmacodynamics of salmeterol against IAV in vivo and in vitro. The results showed that salmeterol could inhibit the activity of three IAV strains (H1N1, H3N2 and H1N1 strain resistant to oseltamivir and amantadine) in the MDCK cells. In vivo, salmeterol could improve the survival state of infected mice, and further mechanism studies shown that salmeterol could improve the pathological characteristics of the lungs, reduce the loads of virus and the expression of M2 and IFITM3 proteins in the lungs of mice. In addition, salmeterol could inhibit the formation of NLRP3 inflammasome, thus reducing the production of the TNF-α, IL-6 and MCP-1 and alleviating inflammatory symptoms. Further results showed that salmeterol can protect A549 cells from cytopathic effect caused by IAV and reduce the production of inflammasome by decreasing the expression of RIG-1 in A549 cells. Finally, salmeterol could improve the spleen morphology and significantly increase the ratio of lymphocyte CD4+/CD8+ to improve immune function of infected mice. In our study, it is confirmed that salmeterol has certain anti-IAV activity through pharmacodynamic study in vivo and in vitro, which lays an important research foundation for the new indication of salmeterol and discovery of new drug against IAV. [ABSTRACT FROM AUTHOR]

• Caspase-1-induced pyroptosis pathway of classical inflammatory vesicles. • Non-classical inflammatory vesicle scorch pathway. • Pyroptosis and digestive system malignancies. • Pyroptosis and non-small cell lung cancer. • The role and mechanism of cell scorching in antitumor therapy. Pyroptosis, also known as cellular inflammatory necrosis, is a programmed cell death mediated by the Gasdermin family of proteins. The mechanisms by which pyroptosis occurs are divided into the GSDMD-mediated Caspase-1 and Caspase-4/-5/-11-dependent classical inflammatory vesicle pathway and the GSDME-mediated Caspase-3 and granzyme-dependent non-classical inflammatory vesicle pathways, among others. Recent studies have shown that pyroptosis has both inhibitory and promotive effects on tumor development. Pyroptosis induction also plays a dual role in antitumor immunotherapy: on the one hand, it suppresses antitumor immunity by promoting the release of inflammatory factors, and on the other hand, it inhibits tumor cell proliferation by triggering antitumor inflammatory responses. In addition, cell scorching plays an essential role in chemotherapy. It has been found that natural drugs modulating the induction of cell scorch are necessary to treat tumors. Therefore, studying the specific mechanisms of cell pyroptosis in different tumors can provide more ideas for developing oncology drugs. In this paper, we review the molecular mechanisms of pyroptosis and the role of pyroptosis in tumor development and treatment to provide new targets for clinical tumor treatment, prognosis, and antitumor drug development. [ABSTRACT FROM AUTHOR]

[Display omitted] • IDO1 induces immune tolerance within TME. • Serum profiling of IDO1 metabolites is of prognostic value. • IDO1 upregulation occurs after ICI therapy. • IDO1 inhibitors can be used safely with ICI therapy. • Epacadostat plus ICI renders promising clinical responses. • Clinical efficacy of anti-PD-L1/IDO inhibitor vaccination is promising. Metabolic alterations occur commonly in tumor cells as a way to adapt available energetic sources for their proliferation, survival and resistance. Indoleamine 2,3-dioxygenase 1 (IDO1) is an intracellular enzyme catalyzing tryptophan degradation into kynurenine. IDO1 expression shows a rise in the stroma of many types of human cancers, and it provides a negative feedback mechanism for cancer evasion from immunosurveillance. Upregulation of IDO1 correlates with cancer aggression, poor prognosis and shortened patient survival. The increased activity of this endogenous checkpoint impairs effector T cell function, increases regulatory T cell (Treg) population and induces immune tolerance, so its inhibition potentiates anti-tumor immune responses and reshapes immunogenic state of tumor microenvironment (TME) presumably through normalizing effector T cell activity. A point is that the expression of this immunoregulatory marker is upregulated after immune checkpoint inhibitor (ICI) therapy, and that it has inducible effect on expression of other checkpoints. These are indicative of the importance of IDO1 as an attractive immunotherapeutic target and rationalizing combination of IDO1 inhibitors with ICI drugs in patients with advanced solid cancers. In this review, we aimed to discuss about the impact of IDO1 on tumor immune ecosystem, and the IDO1-mediated bypass of ICI therapy. The efficacy of IDO1 inhibitor therapy in combination with ICIs in advanced/metastatic solid tumors is also a focus of this paper. [ABSTRACT FROM AUTHOR]

• The OVA sensitized AR mouse model and EOL-1 cells model are established. • The level of miR-223-3p is up-regulated in AR patients and AR mice. • MiR-223-3p affects AR inflammatory response by promoting eosinophil degranulation. • FBXW7 is a target gene of miR-223-3p, and its expression is low in AR group. • MiR-223-3p affects eosinophil degranulation and AR inflammation by targeting FBXW7. MiR-223-3p is a multifunctional microRNA regulated by multiple transcription factors and plays a critical role in inflammation. This paper was designed to investigate the regulatory role and mechanism of miR-223-3p in eosinophils degranulation and allergic rhinitis (AR) inflammation. OVA sensitized AR mouse model and EOL-1 cells model were established. RT-qPCR and FISH were performed to detect the miR-223-3p expression. ELISA and WB were utilized to evaluate mRNA and protein expression. HE staining and transmission electron microscopy were applied to observe the morphological changes in nasal mucosa. Flow cytometry and immunofluorescence staining were performed to measure the proportion of eosinophils and eosinophilic major basic protein expression. The targeting relationship between miR-223-3p and FBXW7 was verified by bioinformatic analysis and dual-luciferase reporter gene assay. The expression of FBXW7 was detected by immunohistochemistry. The level of miR-223-3p in nasal mucosa was significantly up-regulated in AR group. The expression of miR-223-3p, ECP, MBP, and EPO were increased in EOL-1 cells, further increasing the miR-223-3p level could promote the ECP and EPO mRNA expression. Upregulation of miR-223-3p increased eosinophils granule protein expression, aggravated mucosal destruction and enhanced AR inflammation. Luciferase assay verified miR-223-3p directly target the 3ʹ-UTR of FBXW7. In vitro, overexpression of FBXW7 could reverse the increase in MBP expression caused by the up-regulation of miR-223-3p. In vivo, knockdown of FBXW7 could reverse the down-regulation in granule protein level caused by the down-regulation of miR-223-3p, thereby aggravating AR inflammation. Collected evidence elucidated that miR-223-3p could regulate the eosinophil degranulation and enhances the inflammation in AR by targeting FBXW7. The miR-223-3p/FBXW7 axis may provide a novel approach for AR treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] • SARS-CoV-2 promotes an inflammatory phenotype in human monocytes. • In SARS-CoV-2 stimulated PBMC Tα1 mitigates monocyte and myeloid DC activation. • Tα1 dampens SARS-CoV-2 mediated induction of pro-inflammatory cytokines. • Tα1 promotes release of the anti-inflammatory factors IL-10 from SARS-CoV- 2-stimulated PBMC. The peculiar property of Thymosin alpha 1 (Tα1) to act as master regulator of immune homeostasis has been successfully defined in different physiological and pathological contexts ranging from cancer to infection. Interestingly, recent papers also demonstrated its mitigating effect on the "cytokine storm" as well as on the T-cell exhaustion/activation in SARS-CoV-2 infected individuals. Nevertheless, in spite of the increasing knowledge on Tα1-induced effects on T cell response confirming the distinctive features of this multifaceted peptide, little is known on its effects on innate immunity during SARS-CoV-2 infection. Here, we interrogated peripheral blood mononuclear cell (PBMC) cultures stimulated with SARS-CoV-2 to disclose Tα1 properties on the main cell players of early response to infection, namely monocytes and myeloid dendritic cells (mDC). Moving from ex vivo data showing an enhancement in the frequency of inflammatory monocytes and activated mDC in COVID-19 patients, a PBMC-based experimental setting reproduced in vitro a similar profile with an increased percentage of CD16+ inflammatory monocytes and mDC expressing CD86 and HLA-DR activation markers in response to SARS-CoV-2 stimulation. Interestingly, the treatment of SARS-CoV-2-stimulated PBMC with Tα1 dampened the inflammatory/activation status of both monocytes and mDC by reducing the release of pro-inflammatory mediators, including TNF-α, IL-6 and IL-8, while promoting the production of the anti-inflammatory cytokine IL-10. This study further clarifies the working hypothesis on Tα1 mitigating action on COVID-19 inflammatory condition. Moreover, these evidence shed light on inflammatory pathways and cell types involved in acute SARS-CoV-2 infection and likely targetable by newly immune-regulating therapeutic approaches. [ABSTRACT FROM AUTHOR]

• Antibody-based therapies for glioma are promising with high specificity. • Antibody targets include surface markers, angiogenesis and immunosuppressive signals. • BBB limits the treatment efficacy of anti-glioma antibodies. • BBB penetration methods include receptors, nanodelivery, and physical/chemical ways. Gliomas are highly invasive and are the most common type of primary malignant brain tumor. The routine treatments for glioma include surgical resection, radiotherapy, and chemotherapy. However, glioma recurrence and patient survival remain unsatisfactory after employing these traditional treatment approaches. With the rapid development of molecular immunology, significant breakthroughs have been made in targeted glioma therapy and immunotherapy. Antibody-based therapy has excellent advantages in treating gliomas due to its high specificity and sensitivity. This article reviewed various targeted antibody drugs for gliomas, including anti-glioma surface marker antibodies, anti-angiogenesis antibodies, and anti-immunosuppressive signal antibodies. Notably, many antibodies have been validated clinically, such as bevacizumab, cetuximab, panitumumab, and anti-PD-1 antibodies. These antibodies can improve the targeting of glioma therapy, enhance anti-tumor immunity, reduce the proliferation and invasion of glioma, and thus prolong the survival time of patients. However, the existence of the blood–brain barrier (BBB) has caused significant difficulties in drug delivery for gliomas. Therefore, this paper also summarized drug delivery methods through the BBB, including receptor-mediated transportation, nano-based carriers, and some physical and chemical methods for drug delivery. With these exciting advancements, more antibody-based therapies will likely enter clinical practice and allow more successful control of malignant gliomas. [ABSTRACT FROM AUTHOR]

[Display omitted] • Virulence of different SARS-CoV-2 variants including Alpha, Beta, Gamma, Epsilon, Zeta, Eta, Theta, Lota, Kappa, Lambda, Mu, Delta and vaccine effectiveness against them. • Virulence of the currently circulating variant of concern (VOC), the Omicron variant, and vaccine effectiveness against it. • Discussion of the effectiveness of parental vs. bivalent mRNA vaccines against new SARS-CoV-2 sublineages. It has been more than three years since the first emergence of coronavirus disease 2019 (COVID-19) and millions of lives have been taken to date. Like most pandemics caused by viral infections, massive public vaccination is the most promising approach to cease COVID-19 infection. In this regard, several vaccine platforms including inactivated virus, nucleic acid-based (mRNA and DNA vaccines), adenovirus-based, and protein-based vaccines have been designed and developed for COVID-19 prevention and many of them have received FDA or WHO approval. Fortunately, after global vaccination, the transmission rate, disease severity, and mortality rate of COVID-19 infection have diminished significantly. However, a rapid increase in COVID-19 cases due to the omicron variant in vaccinated countries has raised concerns about the effectiveness of these vaccines. In this review, articles published between January 2020 and January 2023 were reviewed using PubMed, Google Scholar, and Web of Science search engines with appropriate related keywords. The related papers were selected and discussed in detail. The current review mainly focuses on the effectiveness and safety of COVID-19 vaccines against SARS-CoV-2 variants. Along with discussing the available and approved vaccines, characteristics of different variants of COVID-19 have also been discussed in brief. Finally, the currently circulating COVID-19 variant i.e Omicron, along with the effectiveness of available COVID-19 vaccines against these new variants are discussed in detail. In conclusion, based on the available data, administration of newly developed bivalent mRNA COVID-19 vaccines, as booster shots, would be crucial to prevent further circulation of the newly developed variants. [ABSTRACT FROM AUTHOR]

• IL-17A involved in progression of ischemic stroke risk factors and contributes to poor prognosis. • In the acute phase of ischemic stroke, IL-17A exacerbates the extent of the acute inflammatory response and tissue damage. • New perspective suggests that IL-17A promotes neurological repair in the recovery phase of ischemic stroke. • Targeted IL-17A therapy may be beneficial for ischemic stroke patients. Interleukin-17A (IL-17A) plays an important role in the progression of ischemic stroke. IL-17A mediates the endothelial inflammatory response, promotes water and sodium retention, and changes the electrophysiological structure of the atrium, accelerating the progression of ischemic stroke risk factors such as atherosclerotic plaques, hypertension, and atrial fibrillation. In the acute phase of ischemic stroke, IL-17A mediates neuronal injury through neutrophil chemotaxis to the site of injury, the induction of neuronal apoptosis, and activation of the calpain-TRPC-6 (transient receptor potential channel-6) pathway. During ischemic stroke recovery, IL-17A, which is mainly derived from reactive astrocytes, promotes and maintains the survival of neural precursor cells (NPCs) in the subventricular zone (SVZ), neuronal differentiation, and synapse formation and participates in the repair of neurological function. Therapies targeting IL-17A-associated inflammatory signaling pathways can reduce the risk of ischemic stroke and neuronal damage and are a new therapeutic strategy for ischemic stroke and its risk factors. In this paper, we will briefly discuss the pathophysiological role of IL-17A in ischemic stroke risk factors, acute and chronic inflammatory responses, and the potential therapeutic value of targeting IL-17A. [ABSTRACT FROM AUTHOR]

• Erenumab has remarkable efficacy in short and long-term treatment of migraine. • The efficacy of Erenumab initiated at the first week of administration. • Erenumab has favorable effect in combination therapy with other preventive drugs. This systematic review aims to show the efficiency of Erenumab in the preventive therapy of episodic and chronic migraine, which is still under research. Migraine is a chronic neurovascular disorder that causes disability and a social burden. There are various medications used for migraine prevention regimens, most of which have unwanted side effects and aren't often quite effective. Erenumab is a monoclonal antibody that targets calcitonin gene-related peptide receptors and was recently approved by the Food and Drug Administration for migraine prevention. For this systematic review, we searched through Scopus and PubMed databases using "Erenumab" or "AMG 334" and "migraine" as keywords, and all the studies from 2016 to March 18, 2022, were included. Original English articles assessing any outcomes referring to the efficacy of Erenumab in migraine headache treatment were included in this study. We found 53 out of 605 papers eligible to be investigated. Erenumab in both dosages of 70 mg and 140 mg could decrease the mean of monthly migraine days and monthly acute migraine-specific medication days. Erenumab also has a higher rate of ≥ 50 %, ≥ 75 %, and 100 % reduction in monthly migraine days from the baseline in different regions. The efficacy of Erenumab was initiated in the first week of administration and sustained throughout and after treatment. Erenumab was also potent in the treatment of migraine with allodynia, aura, prior preventive therapy failure, medication overuse headache, and menstrual migraine. Erenumab also had favorable outcomes in combination therapy with other preventive drugs like Onabotulinumtoxin-A. Erenumab had remarkable efficacy in the short and long-term treatment of episodic and chronic migraine, notably the patients with difficult-to-treat migraine headaches. [ABSTRACT FROM AUTHOR]

• Moderate and severe symptoms are very rare in the US and Hamamatsu in Japan. • There is no difference on COVID-19 effectiveness between vaccinated and unvaccinated. • The CDC dataset showed the effectiveness of vaccination prior to the Omicron variant. This paper examines effectiveness of vaccination with symptoms by age groups in the US and Hamamatsu city in Japan. The efficacy of vaccination has been reported in Singapore, but both datasets such as the US CDC dataset and the Hamamatsu dataset contradict the Singapore results. Both local government and government datasets are publicly available for peer review and reader validation. [ABSTRACT FROM AUTHOR]

• EuDH1 is a non-steroidal anti-inflammatory drug with a novel structure that can release hydrogen sulfide gas signaling molecules. • EuDH1 has potent anti-inflammatory activity in vitro and in vivo. • EuDH1 plays an anti-inflammatory role by regulating the NLRP3 inflammasome pathway. • EuDH1 has a protective effect on NLRP3 inflammasome-driven acute liver and lung injury. • EuDH1 can act as an inhibitor of NLRP3 inflammasome, providing a new candidate for the treatment of related diseases. Non-steroidal anti-inflammatory drugs (NSAIDs) possessing anti-inflammatory, analgesic and antipyretic activities, are widely used in the treatment of osteoarthritis, rheumatism and rheumatoid arthritis. However, its long-term or large use will cause serious gastrointestinal injury or cardiovascular adverse reactions, which limits its clinical application. We have synthesized a new class of NSAIDs, EuHD1, which can release hydrogen sulfide and have better gastrointestinal safety. However, the anti-inflammatory molecular mechanism of the drug is still unclear. In this paper, we explored the mechanism of EuHD1 on NLRP3 inflammasome and its effects on acute lung injury and acute liver injury in mice. In vitro results demonstrated that EuHD1 inhibited macrophage pyroptosis and LDH release induced by LPS combined with ATP. In addition, EuHD1 blocked NLRP3 inflammasome activation and suppressed following Caspase-1 activation and secretion of mature IL-1β. EuHD1 restrained intracellular ROS production and the formation of ASC oligomers, which inhibited the assembly and activation of NLRP3 inflammasome. In vivo results further showed that EuHD1 alleviated LPS-induced acute lung injury in mice, and inhibited the production of mature IL-1β and Caspase-1 (p20). Besides, EuHD1 improved D-GalN/LPS-induced acute liver injury, and inhibited SOD/MDA levels and oxidative stress injury, and blocked the activation of NLRP3 inflammasome. In summary, we found that EuHD1 inhibits the assembly and activation of NLRP3 inflammasome through restraining the production of ROS and the formation of ASC oligomers, and has therapeutic effects on acute lung injury and liver injury in mice, indicating that EuHD1 has the potential to treat NLRP3 inflammasome-related diseases. [ABSTRACT FROM AUTHOR]

• The etiology of endometriotic pain is unknown, and the pain is now classified as a neuroinflammatory pain. This paper is aimd to better understand pathogenesis from the standpoint of neuroimmunity. • The primary function of Ninjurin is related to the underlying mechanism of endometriosis pain. • Ninjurin might be a novel way for non-hormonal endometriosis therapy. Further open new avenues for comprehensive neuroimmune therapy. Endometriosis remains a widespread but severe gynecological disease in women of reproductive age, with an unknown etiology and few treatment choices. The menstrual reflux theory is largely accepted as the underlying etiology but does not explain the morbidity or unpleasant pain sensations of endometriosis. The neurological and immune systems are both involved in pain mechanisms of endometriosis, and interlinked through a complex combination of cytokines and neurotransmitters. Numerous pieces of evidence suggest that the nerve injury-inducible protein, Ninjurin, is actively expressed in endometriosis lesions, which contributes to the etiology and development of endometriosis. It may be explored in the future as a novel therapeutic target. The aim of the present review was to elucidate the multifaceted role of Ninjurin. Furthermore, we summarize the association of Ninjurin with the pain mechanism of endometriosis and outline the future research directions. A novel therapeutic pathway can be discovered based on the potential pathogenic variables. [ABSTRACT FROM AUTHOR]

• We systematically and in detail summarize the classification and biological characteristics of DC, as well as its development process. We focus on and deeply understand the role of DC in regulating the pathogenesis of different allergic diseases. • We demonstrate for the frist time the role of dendritic cells in various allergic diseases including AR, AA, AD, and FA. • Based on inflammatory response and immune regulation, a better understanding of the role of DC in immunomodulation and Th2 immune response can guide the development of new therapeutic targets for various allergic diseases and provide new ideas for the treatment of patients with allergic diseases. Allergic diseases are important diseases that affect many patients worldwide. Over the past few decades, the incidence of allergic diseases has increased significantly due to social development and increased environmental degradation, which has placed a huge economic burden on public health and even led to an increase in mortality. Substantial progress has been made in the understanding of the mechanisms of allergic diseases, and past studies have shown that the occurrence and development of allergic diseases are closely related to changes in the state of the immune system. With the study and in-depth understanding of innate immune lymphocytes, researchers have gradually discovered that dendritic cells (DC) play an important role in many allergic diseases. DC are the body's main antigen-presenting cells, which ingest, process, and hand allergens, and then secrete chemokines such as chemokine ligands 17(CCL17), CCL22, and upregulate their own surface co-stimulating molecules. Then DC present the antigen peptide to the initial T cells and further differentiate them into helper T cells 2(Th2). As an important part of humoral immunity, Th2 participates in the regulation of type 2 immune response through the secretion of cytokines such as interleukin 4(IL-4), IL-5, and IL-13 and plays a leading role. However, our current research on DC is limited and its status in allergic diseases is unclear.Among them, allergic rhinitis, allergic asthma, atopic dermatitis, and food allergy are DC-mediated Th2 immune-related factor disorder-related allergic diseases, and some progress has been made in recent years in the study of the pathogenesis of these diseases. This paper outlines the common phenotypes and activation pathways of DC in different allergic diseases as well as potential research directions to improve the understanding of its immunomodulatory role in different allergic diseases and ultimately find new ways to treat these diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] • TME and glycolysis promote the occurrence and metastasis of tumors. • The mRNA vaccine activates CTL, cooperative NK, and M1 cells to improve the TIME. • Using vectors enhances the anti-tumor effect of the mRNA vaccine by improving TIME. • An mRNA vaccine combined with adjuvants or ICIs inhibits tumor metastasis. With the increasing threat of tumors to humans, mRNA vaccine-based immunotherapy has received extensive attention; however, the killing effect is sometimes unsatisfactory. The occurrence of tumors is closely related to the abnormality of the tumor immune microenvironment, including the increase in the number of immunosuppressive cells, the anomaly of some cells with tumor-killing function, and the increase in the glycolysis pathway, all of which will affect the anti-tumor effect of mRNA vaccines. Furthermore, delivery in the body and successful escape from lysosome are also essential steps that involve the result of killing. Starting from inhibiting tumor growth and metastasis by mRNA vaccines, this paper summarizes the tumor microenvironment constructed by immunosuppressive cells and cytokines, which inhibit immune cells from exerting anti-tumor effects, emphasizing the increase of glycolytic pathway after tumor formation, which makes tumors have a high probability of metastasis. In the present study, mRNA vaccines adjust the number of immune cells by combining adjuvants or immune checkpoint inhibitors (ICIs), thereby improving the tumor immune microenvironment (TIME) and tilting the balance in favor of immune-potent cells can achieve better anti-tumor effects. All efforts to understand the relationship between TIME and mRNA vaccine will provide a basis for tumor treatment in the future. [ABSTRACT FROM AUTHOR]

• Recently, the emergence of MPX has created a global threat, and vaccination is one of the significant ways to fight against the virus. • The article describes the important points and issues for vaccines and vaccinations related to the MPXV. • It also illustrates significant research on the MPXV, especially smallpox vaccines, and its outcome in MPX infection. • Vaccination preparedness has been illustrated in various countries like the USA, UK, Canada, Denmark, Germany, etc. The recent emergence of monkeypox (MPX) has created a global threat. The number of infected and suspected cases of MPX is increasing in different parts of the world, especially in non-African countries. However, vaccines are available to fight against this disease. It has been observed that smallpox vaccines can be used to protect against MPX. The present article highlights the significant points and various issues for vaccines and vaccinations that should be considered related to MPX. This paper illustrates current vaccines for smallpox that can be utilized to protect against MPX infection. The article also describes the different significant research on MPXV, especially smallpox vaccines, and its outcome in MPX infection. We have also tried to depict the smallpox vaccination eradication model through the statistical interface using smallpox eradication data from Central and West Africa between 1967 and 1972. We suggest that these models might be helpful for the eradication of MPX in the middle to low-economic countries. Simultaneously, we have also discussed vaccination preparedness in different countries like the USA, UK, Canada, Denmark, Germany, etc. Our report might be helpful to scientists and policymakers in understanding the vaccines and vaccination against MPX and formulating effective strategies to fight against the disease. [ABSTRACT FROM AUTHOR]

• Application and design strategy of different CAR cells in solid tumors. • Improving the CAR costimulatory domain architecture might overcome solid tumor immunosuppressive microenvironmental barriers. • CAR cell therapy will become an important part and the future direction of solid tumor immunotherapy. In addition to chimeric antigen receptor (CAR)-αβ T -cell therapy, CAR-NK, CAR-NKT, CAR-M and CAR-γδ T -cell therapy have gradually been applied to the treatment of solid tumors. Compared to hematological tumors, solid tumors have the characteristics of strong tumor heterogeneity, limited target antigen selection, and low T -cell infiltration to build immunosuppressive tumor microenvironment. These features would present great obstacles to CAR cell therapy. This paper comprehensively analyzed the application of different CAR cells to solid tumors and summarized the design principles of different CAR cells to provide the direction for the development of CAR cell therapy in solid tumors. [ABSTRACT FROM AUTHOR]

• All subtypes of HLA-B27 form high molecular weight (HMW) aggregates. • HMW species of non-disease associated (non-DA) subtypes are prone to degradation. • The non-DA subtypes undergo significant loss of secondary structure at pH 4.0. • The disease-associated (DA) subtypes continue to retain structure at pH 4.0. • DA heavy chains and LAMP1 co-localize, and persist upon autophagy induction. Several hypotheses have been proposed to explain the high rate of disease association of HLA-B27 with ankylosing spondylitis (AS), including formation of disulfide-bonded dimers and misfolding of the heavy chain (HC), involving formation of high molecular weight (HMW) multimers. Recently, we have shown that the HMW entities of non-disease associated (non-DA) subtypes cause activation of endosomal-lysosomal pathways, while disease-associated (DA) subtypes of HLA-B27 cause activation of autophagy and unfolded protein response (UPR) pathways. In this paper, we seek an explanation for the failure of these pathways to degrade the HMW entities of DA subtypes of HLA-B27, using a combination of in vitro assays, using extracellular domains of heavy chains (EDHC), as well as in vivo assays, using stable transfectants of the full lengths of heavy chains (FLHC) of DA and non-DA subtypes. Our data shows that both DA and non-DA subtypes form HMW entities. However, non-DA HMW entities display far greater levels of degradation than DA HMW species. Non-DA EDHC display greater loss of structure at lysosomal pH in vitro. This was confirmed by experiments showing that (i) DA FLHCs co-localize with LAMP1, and (ii) induction of autophagy by rapamycin causes significant decrease in levels of non-DA HMW entities, but not that of DA HMW entities. These results point towards lack of facile lysosomal clearance of FLHCs of DA subtypes, suggesting that disease association of HLA-B27 subtypes is correlated with higher persistence of HMW entities in the low pH of lysosomes, with higher potential to trigger immune response. [ABSTRACT FROM AUTHOR]

• We described the roles of circulating tumor DNA (ctDNA) in tumor immunotherapy at length. • The detection methods of ctDNA in various tumors were summarized with Immune checkpoint blockade (ICB) points and mutation genes. • The advantages and inherent limitations of immunotherapy were compared. • Detailed and vivid diagrams and tables were useful to illustrate the roles of ctDNA compared with tissue biopsy and imagological examination. • This paper provides a direction for future research of ctDNA to facilitate the application of ctDNA in tumor patients for diagnoses, prognoses, and guidance for treatments. Circulating tumor DNA (ctDNA) sequencing holds considerable promise for early diagnosis and detection of surveillance and minimal residual disease. Blood ctDNA monitors specific cancers by detecting the alterations found in cancer cells, such as apoptosis and necrosis. Due to the short half-life, ctDNA reflects the actual burden of other treatments on tumors. In addition, ctDNA might be preferable to monitor tumor development and treatment compared with invasive tissue biopsy. ctDNA-based liquid biopsy brings remarkable strength to targeted therapy and precision medicine. Notably, multiple ctDNA analysis platforms have been broadly applied in clinical immunotherapy. Through targeted sequencing, early variations in ctDNA could predict response to immune checkpoint inhibitor (ICI). Several studies have demonstrated a correlation between ctDNA kinetics and anti-PD1 antibodies. The need for further research and development remains, although this biomarker holds significant prospects for early cancer detection. This review focuses on describing the basis of ctDNA and its current utilities in oncology and immunotherapy, either for clinical management or early detection, highlighting its advantages and inherent limitations. [ABSTRACT FROM AUTHOR]

• So far, a particular therapeutic option has not been approved for COVID-19. • Antiviral agents and immune modulating strategies has been studied for COVID-19 treatment. • Current treatments are diverse in each patient and have various outcomes. • Some novel approach such as cell based therapy, and immunotherapy may have significant potential in the COVID-19 treatment. Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is a highly pathogenic and transmissible virus. Infection caused by SARS-CoV-2 known as Coronavirus disease 2019 (COVID-19) can be severe, especially among high risk populations affected of underlying medical conditions. COVID-19 is characterized by the severe acute respiratory syndrome, a hyper inflammatory syndrome, vascular injury, microangiopathy and thrombosis. Antiviral drugs and immune modulating methods has been evaluated. So far, a particular therapeutic option has not been approved for COVID-19 and a variety of treatments have been studied for COVID-19 including, current treatment such as oxygen therapy, corticosteroids, antiviral agents until targeted therapy and vaccines which are diverse in each patient and have various outcomes. According to the findings of different in vitro and in vivo studies, some novel approach such as gene editing, cell based therapy, and immunotherapy may have significant potential in the treatment of COVID-19. Based on these findings, this paper aims to review the different strategies of treatment against COVID-19 and provide a summary from traditional and newer methods in curing COVID-19. [ABSTRACT FROM AUTHOR]

• In this work, we evaluated the mechanisms by which IL-6 and HIF-1α induce bone destruction in rheumatoid arthritis (RA). • And the JAK/STAT signaling pathway involved in bone destruction. • The current JAK/STAT inhibitors for RA bone destruction were also discussed. Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic joint inflammation and bone erosion. The bones in the human body are constantly undergoing bone remodeling throughout their lives, which is the process of bone resorption by osteoclasts to damaged bone tissue and new bone formation by osteoblasts. Osteoblasts (OBs) are the main functional cells in bone formation, responsible for the synthesis, secretion and mineralization of the bone matrix. On the contrary, osteoclasts (OCs) mediate bone breakdown during natural bone turnover, but excessive breakdown occurs in RA. Under the condition of RA inflammation, many molecules, such as IL-1β, IL-6, TNF-α, IL-17 and hypoxia-inducible factor-1α (HIF-1α) are produced that could mediate bone loss. Studies have shown that cytokines mainly promote the formation of OCs and play a role in bone resorption by stimulating OBs to express receptor activator of NF-κB ligand (RANKL). JAK/STAT plays a crucial role in the process of bone destruction. And JAK/STAT pathway mediates the RANKL/receptor activator of NF-κB (RANK)/osteoprotegerin (OPG) axis. Tofacitinib, Baricitinib, Peficitinib and Filgotinib are now being used in patients with moderate to severe RA, as well as in patients with RA who have an inadequate response to methotrexate therapy and bone destruction. Currently, Tofacitinib and Baritinib are approved for the treatment of moderate-to-severely active RA. JAK inhibitors have been reported to have better efficacy and lower adverse effects compared with methotrexate and adalimumab. In addition, two JAK inhibitors are currently in development: the JAK1 selective Upadacitinib, and the JAK3 selective inhibitor Decernotinib. In addition to the above JAK inhibitors, some small molecular compounds inhibit bone destruction by inhibiting the Phosphorylation of STAT3. In this paper, the research progress of bone destruction participated by JAK/ STAT in rheumatoid arthritis and therapeutic effect of JAK/STAT inhibitors were reviewed. [ABSTRACT FROM AUTHOR]

• The key points of this review are as follows: • We focused on different pathways of the mechanisms by which gut microbiota regulates bone mass, in particular the effect of metabolites of gut microbiota on bone mass. • We should pay more attention to the role of diet, probiotics, prebiotics, and fecal microbiota transplantation in the prevention and treatment of menopausal osteoporosis. Postmenopausal osteoporosis (PMO) results from a reduction in bone mass and microarchitectural deterioration in bone tissue due to estrogen deficiency, which may increase the incidence of fragility fractures. The number of people suffering from PMO has increased over the years because of the rapidly aging population worldwide. However, several pharmacological agents for the treatment of PMO have many safety risks and impose a heavy financial burden to patients and society. In recent years, the "gut-bone" axis has been proposed as a new approach in the prevention and treatment of PMO. This paper reviews the relationship between the gut microbiota and PMO, which mainly includes the underlying mechanisms between hormones, immunity, nutrient metabolism, metabolites of the gut microbiota and intestinal permeability, and explores the possible role of the gut microbiota in these processes. Finally, we discuss the therapeutic effects of diet, prebiotics, probiotics, and fecal microbiota transplantation on the gut microbiota. [ABSTRACT FROM AUTHOR]

[Display omitted] • TREM2 is a potential therapeutic target for the treatment of stroke. • TREM2 could regulate the phenotype of microglia. • TREM2 has important effects on energy metabolism, phagocytosis and anti-inflammatory function of microglia. Microglia are the earliest activated and the longest lasting immune cells after stroke, and they participate in almost all the pathological reactions after stroke. However, their regulatory mechanism has not been fully elucidated. Triggering receptor expressed on myeloid cells-2 (TREM2) is a cell surface receptor that is mainly expressed in microglia of the central nervous system. The receptor plays an important role in regulating microglia energy metabolism and phenotypic transformation. At present, TREM2 has been developed as a potential target for AD, coronary atherosclerosis and other diseases. However, TREM2 does not provide a systematic summary of the functional transformation and intrinsic molecular mechanisms of microglia after stroke. In this paper, we have summarized the functional changes of TREM2 in microglia after stroke in recent years, and found that TREM2 has important effects on energy metabolism, phagocytosis and anti-inflammatory function of microglia after stroke, suggesting that TREM2 is a potential therapeutic target for the treatment of stroke. [ABSTRACT FROM AUTHOR]

• New advancement for development of optimal and safe delivery route for oncolytic viruses. • Diverse platforms, such as employment of cells and nanoparticles to protect the virus from antiviral neutralization and improve the oncolytic potential of viruses. • Efficient systematic delivery of oncolytic viruses enables the expansion of their application toward cancer therapy. • Development of novel methods to make oncolytic viruses more resistant to undesirable reactions of the host's immune system. Oncolytic viruses (OVs) harness the hallmarks of tumor cells and cancer-related immune responses for the lysis of malignant cells, modulation of the tumor microenvironment, and exertion of vaccine-like activities. However, efficient clinical exploitation of these potent therapeutic modules requires their systematic administration, especially against metastatic and solid tumors. Therefore, developing methods for shielding a virus from the neutralizing environment of the bloodstream while departing toward tumor sites is a must. This paper reports the latest advancements in the employment of chemical and biological compounds aimed at safe and efficient delivery of OVs to target tissues or tumor deposits within the host. [ABSTRACT FROM AUTHOR]

• Adhesion GPCRs are highly expressed in UCEC. • Adhesion GPCRs are associated with prognosis of UCEC. • Immune cell infiltration of adhesion GPCRs in UCEC patients. • ADGRF1 could be a potential therapeutic target for UCEC. Adhesion G protein-coupled receptors (adhesion GPCRs), as a member of the G protein-coupled receptors (GPCRs) superfamily, have gradually entered the field of vision of researchers. The structure, function, and involvement of adhesion GPCRs in cancer development have been discussed in a series of papers. Uterine Corpus Endometrial Carcinoma (UCEC) is a malignant tumor of endometrium epithelial, which is also one of the most common female reproductive system tumors, but there are few pieces of research related to adhesion GPCRs in UCEC. In the current study, the UALCAN, GEPIA, Kaplan-Meier Plotter, MethSurv, SurvivalMeth, cBioPortal, String, GeneMANIA, DAVID, TRRUST, and Timer databases were used to examine the expression patterns and probable roles of adhesion GPCR family in UCEC. The expression levels of ADGRC1, ADGRC3, ADGRE1, ADGRF1, ADGRF2, ADGRF3, ADGRF4, ADGRG1, ADGRG5, ADGRG7, and ADGRV1 were significantly elevated in UCEC tissues, and the expression of ADGRC3 and ADGRF1 was significantly correlated with the pathological stage of UCEC. In patients with UCEC, ADGRA3, ADGRB1, ADGRB2, ADGRB3, ADGRC3, ADGRD2, ADGRF1, ADGRF2, ADGRF4, ADGRG1, ADGRG2, ADGRG4, ADGRG6, ADGRG7, ADGRL1, ADGRL2, and ADGRL3 had played important roles in patients' overall survival (OS), with a high expression suggesting shorter OS; while high levels of ADGRC2, ADGRD2, ADGRG7, and ADGRL2 suggested lower relapse-free survival (RFS). Furthermore, the prognostic value of the adhesion GPCRs gene individual CpG, as well as DNA methylation, was also analyzed; however, DNA methylation profiling demonstrated no significant correlation between the methylation level of adhesion GPCRs and the prognosis. The neighbor gene interaction analysis and enrichment analysis were also implemented to detect the possible mechanism. In addition, we found a correlation between the adhesion GPCRs and immune infiltrating cells, and the Cox proportional risk model of adhesion GPCRs with six immune cells showed that ADGRA1, ADGRF1, and ADGRG3 were closely connected with the clinical manifestations of UCEC patients. The adhesion GPCRs, especially ADGRF1, might be used as immunotherapeutic targets and prognostic markers of UCEC. [ABSTRACT FROM AUTHOR]

• Mechanism of NLRP3 inflammasome activation. • Mechanism of mitochondrial DNA in NLRP3 inflammasome activation. • The crosstalk with the process of mitochondrial DNA and the other ways in NLRP3 inflammasome activation. As an intracellular polyprotein complex, the NLRP3 inflammasome is activated by NLRP3 perceiving pathogen-related molecular patterns, damage-related molecular patterns(DAMPs), which will result in the secretion of the caspase1-dependent pro-inflammatory cytokines IL1β and IL18, and the cleavage of GSDMD-mediated pyroptosis. Therefore, inflammasome signaling is tightly regulated. Intracellular and extracellular mitochondria DNA (mtDNA) play different roles in activating the NLRP3 inflammasome. Intracellular mtDNA is easily oxidized and transferred to the cytoplasm, and directly binds to NLRP3 to activate NLRP3 inflammasome, the extracellular mtDNA is involved in the priming and activation of NLRP3 inflammasome as a DAMP; which is related to the occurrence and development of plentiful diseases. In this paper, we will discuss how mitochondrial DNA activates the NLRP3 inflammasome and how the process of activating NLRP3 inflammasome by mtDNA interacts with other NLRP3 inflammasome activation models. [ABSTRACT FROM AUTHOR]

• High-dose radiation can improve mouse survival through regulating the T cells stemness in tumor micro-environment. • This paper is the first time proposed that radiation can enhance the expression of TCF-1 + T cells through cGAS/STING axis. • The study provides evidence for the rational combination of radiation and STING agonists. Radiotherapy is a very effective cancer treatment, mainly through inducing DNA damage of cancer cells. Meanwhile, there is evidence that irradiation can also mobilize tumor-specific immunity, and recent investigations demonstrate that the efficiency of local high-dose radiotherapy is attributable to the presence of CD8+T cells. Here, we observed that high-dose radiation remarkably increased the enrichment of stem cell-like CD8+T cells. Moreover, cGAS/STING signaling augmented stem cell-like CD8+T cells and T stem-like central memory CD8+T cells in a mice tumor model after radiation. These findings raise our understanding of stem cell-like CD8+T cells after radiation stimulation and improve radiation therapy by driving the cGAS/STING signaling pathway for cancer multimodality therapy. [ABSTRACT FROM AUTHOR]

[Display omitted] • Quinolone antibiotics, as commonly used human and animal antibiotics, are widely residual in the environment, and the immunotoxicity study for quinolones is of great importance. • Quinolone antibiotics acting on RAW264.7 macrophages at concentrations of 0.01, 0.1, 1, 10, 100, and 1000 μg/L exhibited a low-dose excitatory hormesis effect, which was demonstrated by activity assays, migration assays, and phagocytosis assays. • The dose that exerts excitatory effect was found to induce macrophage polarization of M1 type by ELISA and Western blot assay, and 0.1 μg/L was selected for mechanism study to explore the relationship between hormesis effect and polarization. • Mechanistic studies have confirmed that when quinolone antibiotics at 0.1 μg/L induce the release of inflammatory factors through PI3K/Akt, Notch1, JNK and JAK2/STAT3 signaling pathways, leading to inflammation. In order to eliminate inflammation, macrophages increase the number of feedback and enhance the migration and phagocytosis functions. • Environmental residual doses of quinolone antibiotics have immunotoxicity. Widespread use of quinolone antibiotics leads to serious residues in the environment and toxicity effects. This paper studied the effects of three typical quinolone antibiotics ciprofloxacin, norfloxacin and pipemidic acid on the polarization of macrophages RAW264.7 cells. The experimental concentrations were 0.01, 0.1, 1, 10, 100 and 1000 μg/L according to the environmental residual level. By MTT assay, phagocytosis assay and migration assay, macrophages were found to exhibit hormesis effect of low dose promotion and high dose inhibition. The detection of macrophages surface markers showed that 0.1 μg/L antibiotics increased the secretion of pro-inflammatory cytokines and induced macrophages to be M1-type, and 1000 μg/L antibiotics significantly increased the secretion of anti-inflammatory cytokines and induced macrophages to be M2-type. In order to explore the relationship between low-dose excitatory effects and polarization, the mechanism of 0.1 μg/L antibiotics inducing macrophages to M1-type was further studied. Results showed that 0.1 μg/L quinolone antibiotics activated the key proteins in the PI3K/Akt, Notch1, JNK and JAK2/STAT3 signaling pathways to cause the secretion of pro-inflammatory cytokines and induce inflammation. In order to eliminate inflammation, macrophages number feedback increased, phagocytosis and migration function enhanced, showing hormesis effect. In vitro macrophages experiment confirmed that quinolone antibiotics with environmental residual concentration had immunotoxicity. [ABSTRACT FROM AUTHOR]

• Biofilm is a community of bacteria embedded in the extracellular matrix that includes 80% of bacterial infections. • The human immune system is not completely effective against biofilm. • Some bacteria use mechanisms by which hijack the host factors to form the biofilm. • Host components like DNA, hyaluronan, collagen, fibronectin, mucin, oligosaccharide moieties, F-actin, plasma, platelet, keratin, sialic acid, laminin, vitronectin, C3- and C4- binding proteins, antibody, proteases, factor I, and factor H have been found to bacterial biofilm formation. Biofilm is a community of bacteria embedded in the extracellular matrix that accounts for 80% of bacterial infections. Biofilm enables bacterial cells to provide particular conditions and produce virulence determinants in response to the unavailability of micronutrients and local oxygen, resulting in their resistance to various antibacterial agents. Besides, the human immune reactions are not completely competent in the elimination of biofilm. Most importantly, the growing body of evidence shows that some bacterial spp. use a variety of mechanisms by which hijack the host components to form biofilm. In this regard, host components, such as DNA, hyaluronan, collagen, fibronectin, mucin, oligosaccharide moieties, filamentous polymers (F-actin), plasma, platelets, keratin, sialic acid, laminin, vitronectin, C3- and C4- binding proteins, antibody, proteases, factor I, factor H, and acidic proline-rich proteins have been reviewed. Hence, the characterization of interactions between bacterial biofilm and the host would be critical to effectively address biofilm-associated infections. In this paper, we review the latest information on the hijacking of host factors by bacteria to form biofilm. [ABSTRACT FROM AUTHOR]